Using stem cells to model health and disease in a dish

A stem cell technique developed over a decade ago that allows scientists to grow many types of cells is bearing fruit in the lab, allowing our neuroscientists to grow a range of brain cells to study development and disease. We spoke to some about its impact on their work.

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Crick scientist Jasmine Harley explains how they grow iPS cells in the lab and how they use them.

When Japanese scientist Shinya Yamanaka announced in 2006 that he had turned mouse skin cells into induced pluripotent stem (iPS) cells, capable of becoming many types of cells, the scientific community looked on in amazement.

The cells were heralded as a breakthrough for regenerative medicine, potentially enabling scientists to use a person’s own skin cells to grow liver, heart or nerve cells to treat disease. This personalised therapy would also have the benefit of avoiding the risk of immune rejection.

Although some progress has been made in the clinical arena, it is biomedical research that has reaped most of the benefits of iPS cell technology in the past 12 years.

Here at the Crick, scientists working in a range of research areas are using the technique to study different cell types and tissues. Their findings are helping them understand the fundamental biology of health and disease.

But arguably, it’s our neuroscientists who have benefited the most from the method, growing and studying nerve cells that were previously available only from post-mortem tissue.

By growing different specialised nerve cells outside of the body, our scientists can follow cells right from early development through to cell death, giving them unprecedented insights into neurodevelopmental and neurodegenerative disorders.

She relies on healthy and genetically modified iPS cells, and iPS cells created from patients with intellectual disabilities, to recapitulate human brain development in a dish and work out when, where and how things work differently.

“The ultimate goal of my research is to find specific genes and molecules associated with intellectual disability that could provide targets for new therapies that go beyond the support that we currently offer,” explains Cristina.

Cristina’s work could also shed light on human brain development and cognition more broadly.

Neurodegeneration in a dish

Motor neurons grown from iPS cells in the lab, viewed down a microscope.

- Jasmine Harley

Rather than focusing on nerve cell development, some of our neuroscientists are using iPS cells to hone in on why nerve cells die in neurodegenerative diseases.

“Before iPS cell technology existed, we relied heavily on post-mortem tissue to study neurodegeneration,” explains Rickie Patani, a clinician scientist who co-runs the Neurodegeneration Biology lab. “It was like being asked to enter a crime scene and work out who committed a crime a hundred years ago.”

“Now, thanks to iPS cells, we’re able to ‘press rewind’ and see the whole crime happening.”

By comparing motor neurons grown from skin cells of patients with motor neurone disease and healthy volunteers, the team is starting to build up a detailed picture of how motor neurons - nerve cells in the brain and spinal cord that control our muscles and allow us to move, talk and breathe - decline and die in the disease.

They are using a similar approach to gain new insights into the potential causes of Parkinson’s disease, by growing cortical neurons that can be studied in the lab.

Future promises and challenges

The potential of iPS cells cannot be underestimated, and Crick neuroscientists are learning more about the nervous system all the time, paving the way for new therapies for both neurodevelopmental and neurodegenerative disorders.

Even 15 years ago it would have been impossible to imagine that we could do what we can today with iPS cells. Rickie Patani

But there remain many roadblocks. As Jasmine Harley, a PhD student in the Neurodegeneration Biology lab explains: “The methods for growing different cell types aren’t always that robust and can be difficult to reproduce in different labs around the world.”

For instance, midbrain dopaminergic neurons, which researchers use to study Parkinson’s disease, have been difficult to grow efficiently and reliably in the lab.

“Some experimental trials have recently been launched that will use patients’ iPS cells as personalised therapy to treat Parkinson’s, but it’s unclear how successful they will be, and it could be many years before we see results,” explains Jasmine.

“For now, we’re most excited about using iPS cells to model disease and screen drugs, to find out if any compounds currently approved for humans are able to prevent or reverse diseases in cells. This is probably our best chance of getting treatments from dish to patient as quickly as possible.”

The technique of growing different cell types from iPS cells is still in its infancy, but looking back at how far we’ve come since their discovery in 2006, who knows what discoveries they’ll facilitate in the coming years.

As Rickie reminds us: “Even 15 years ago it would have been impossible to imagine that we could do what we can today with iPS cells.”

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